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1.
Immunol Lett ; 262: 18-26, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37652189

RESUMO

BACKGROUND: The rise of multi-drug resistant Acinetobacter baumannii poses a grave threat to hospital settings, resulting in increased mortality rates and garnering global attention. The formation of biofilms facilitated by biofilm-associated protein (Bap) and the iron absorption capabilities mediated by Baumannii acinetobactin utilization A (BauA) contribute to the persistence and survival of multidrug-resistant strains. In this study, we aimed to investigate the potential of disrupting the function of BauA and Bap simultaneously as a strategy for controlling A. baumannii. METHODS: Recombinant Bap and BauA were expressed, purified, and subcutaneously administered individually and in combination to BALB/c mice. Subsequently, mice were intraperitoneally challenged with A. baumannii, and the bacterial load and tissue damage in the spleen, lung, and liver were assessed. Serum samples were evaluated to determine antibody titers in surviving mice. RESULTS: Specific IgG antibodies were significantly increased. A combination of the antigens resulted in enhanced titer of specific IgGs in comparison to either BauA or Bap alone. The antibodies remained stable over a seven-month period. The combination of Bap and BauA exhibited superior immunoprotection against A. baumannii infection compared to individual administration, resulting in a further reduction in bacterial load in the liver, spleen, and lungs. The histopathological analysis demonstrated successful protection of the tissues against A. baumannii-induced damage upon administration of the two immunogens. CONCLUSIONS: The combination of Bap and BauA has the potential to target a broader range of A. baumannii strains, including those expressing either Bap or BauA, thereby increasing its efficacy against a diverse array of strains.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Animais , Camundongos , Modelos Animais de Doenças , Anticorpos , Biofilmes , Camundongos Endogâmicos BALB C
2.
Mol Immunol ; 149: 87-93, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35785672

RESUMO

Acinetobacter baumannii is one of the most notorious nosocomial pathogens with high mortality rates. Recently, egg yolk antibody (IgY), has been considered as a promising biomolecule against pneumonia caused by this bacterium. Loop 3 of outer membrane protein 34 (Omp34) was predicted as a highly exposed immunogenic peptide. However, its immunogenicity remains to be experimentally elucidated. In the current study, a construct composed of 5 copies of loop3 of Omp34 labeled as Omp34L3X5 was designed. This construct as well as the recombinant Omp34 were expressed, purified, and injected into laying hens to raise specific antibodies. The specific IgYs were extracted from hyperimmune egg yolks. The Omp34L3X5 and whole cells (WC) of A. baumannii served as antigens in indirect ELISA to assess the purified IgYs reactivity. These antibodies were administered to neutropenic mice 1 h before the challenge with 10 × LD50 of a clinical isolate of A. baumannii. The specific IgYs recognized recombinant Omp34 (P < 0.0001) as well as WC of A. baumannii (P < 0.05). The survival rate of mice that received anti- Omp34L3X5 or anti-Omp34 IgYs was 83.33 % and 100 % respectively. All control mice died within 24 h while mice that received non-specific IgYs died within 72 h. After 24 h, bacterial load in the lung of mice received non-specific IgYs, anti-Omp34L3X5 or anti-Omp34 IgYs were 2.03 × 108, 2.2 × 108, and 1.93 × 108 CFU/organ respectively. Bacterial load in the spleen of mice received non-specific IgYs, anti-Omp34L3X5 or anti-Omp34 IgYs were 1.03 × 108, 7.8 × 107, and 6.3 × 107 CFU/organ respectively. Bacterial load in lung and spleen of control mice were 3.03 × 109 and 1.45 × 108 CFU/organ respectively.


Assuntos
Acinetobacter baumannii , Animais , Proteínas da Membrana Bacteriana Externa , Galinhas , Modelos Animais de Doenças , Gema de Ovo , Feminino , Imunoglobulinas , Camundongos
3.
Int Immunopharmacol ; 108: 108731, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35367743

RESUMO

The complexity of treating Acinetobacter baumannii infections with the newly developed resistant strains has led researchers to confront this pathogen by developing vaccines. In this study, we used two important virulence factors of A. baumannii to elicit immunity against the A. baumannii. The immunogenic loops were from Baumannii acinetobactin utilization A (BauA) and 34kD outer membrane protein (Omp34). C-lobe derivative of the TbpB surface lipoprotein was used to display the superficial epitopes of the TbpA receptor protein of Neisseria meningitidis. The resulting loopless C-lobe (LCL) with implanted nucleotide sequences of the immunogenic loops from BauA and Omp34 was used as a hybrid antigen. The hybrid antigens were expressed in the E. coli and were used to immunize mice. The mice were challenged with a clinical isolate of A. baumannii (ABI022). Immunization with the hybrid antigens of the BauA loop 7 (BauAL7P3), Omp34 loop 3 Omp34L3P1, and the combination of both loops (BauAL7P3Omp34L3P1) brought about 42.86%, 42.86%, and 71.43% protection against A. baumannii infection. Histopathological findings in the immunized mice showed bronchioles clear from inflammatory cells and normal texture of the spleen and liver. The findings support the use of a multivalent vaccine to induce broadly reactive antibody responses against heterologous A. baumannii strains.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Sepse , Infecções por Acinetobacter/prevenção & controle , Animais , Anticorpos Antibacterianos , Antígenos/metabolismo , Proteínas da Membrana Bacteriana Externa , Vacinas Bacterianas , Escherichia coli , Imidazóis , Camundongos , Oxazóis
4.
J Genet Eng Biotechnol ; 20(1): 42, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35254548

RESUMO

BACKGROUND: Efforts toward the development of an effective vaccine against Acinetobacter baumannii, one of the most notorious nosocomial pathogens, are still ongoing. In this regard, virulence factors are interesting targets. Type VI secretion system (T6SS) participates in the pathogenicity of A. baumannii. VgrG is a crucial component of T6SS prevalent among A. baumannii strains. This study was conducted to evaluate the immunoprotectivity of recombinant VgrG (rVgrG) cloned and over-expressed in Escherichia coli BL21 (DE3). BALB/c mice were immunized with the purified rVgrG. Specific anti-VgrG IgG titers were assessed by ELISA. Actively and passively immunized mice were challenged with lethal doses of A. baumannii ATCC 19606. The survival rate, the bacterial burden, and histopathology of tissues in infected mice were examined. RESULTS: Anti-VgrG IgG (p < 0.0001) was significantly increased in immunized mice. No death was seen in actively immunized mice infected with the lethal dose (LD) of 1.9 × 108 CFU of A. baumannii ATCC 19606 within 72 h. Challenge with 2.4 × 108 CFU of the pathogen showed a 75% survival rate. All immunized mice infected with 3.2 × 108 CFU of the pathogen died within 12 h. In passive immunization, no death was observed in mice that received LD of the bacteria incubated with the 1:250 dilution of the immune sera. An increased number of neutrophils around the peribronchial and perivascular areas were seen in unimmunized mouse lungs while passively immunized mice revealed moderate inflammation with infiltration of mixed mononuclear cells and neutrophils. The livers of the unimmunized mice showed inflammation and necrosis in contrast to the livers from immunized mice. Hyperplasia of the white pulp and higher neutrophils were evident in the spleen of unimmunized mice as against the normal histology of the immunized group. CONCLUSIONS: VgrG is a protective antigen that could be topologically accessible to the host antibodies. Although VgrG is not sufficient to be assigned as a stand-alone antigen for conferring full protection, it could participate in multivalent vaccine developments for elevated efficacy.

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